The present invention generally relates to quinoxaline compounds and methods of using them.
Cell proliferation and programmed cell death play important roles in the growth and development of an organism. In proliferative diseases such as cancer, the processes of cell proliferation and/or programmed cell death are often perturbed. For example, a cancer cell may have unregulated cell division through either the overexpression of a positive regulator of the cell cycle or the loss of a negative regulator of the cell cycle, perhaps by mutation. Alternatively, a cancer cell may have lost the ability to undergo programmed cell death through the overexpression of a negative regulator of apoptosis.
One approach to the treatment of human cancers is to target a protein that is essential for cell cycle progression. In order for the cell cycle to proceed from one phase to the next, certain prerequisite events must be completed. There are checkpoints within the cell cycle that enforce the proper order of events and phases. One such checkpoint is the spindle checkpoint that occurs during the metaphase stage of mitosis. Small molecules that target proteins with essential functions in mitosis have the potential to initiate the spindle checkpoint to arrest cells in mitosis. Of the small molecules that arrest cells in mitosis, the majority of those which display anti-tumor activity in the clinic also induce apoptosis. Most compounds known to cause mitotic arrest and apoptosis act as tubulin binding agents. These compounds are believed to alter the dynamic instability of microtubules and indirectly alter the function/structure of the mitotic spindle, thereby causing mitotic arrest. Because most of these compounds target the tubulin protein, a component of all microtubules, they can also affect normal cellular processes in which microtubules have a role.
In view of the foregoing, a need exists for small molecules that target proteins associated with proliferating cells.